Phase 2B Study Data for 4-Week TKA Analgesic

Results from a Phase 2B study of a novel, ultra-sustained pain management for post total knee arthroplasty (TKA) pain management and recuperation drug have been announced. The study, which took place at 13 sites in Australia, Canada, and the United Kingdom, determined that this new compound, ATX101, achieved “sustained post-surgical pain relief for up to four weeks for patients following total knee arthroplasty (TKA) and outperformed a standard of care active comparator, bupivacaine, on durability of effect, use of opioids to support pain relief and the potential for patients to return to day-to-day activities earlier.”

ATX101 is a novel configuration of a bioresorbable polymer and bupivacaine that contains a high density of bupivacaine within a biodegradable polymer designed to deliver an ultra-sustained analgesic effect over weeks before dissolving.

Study participants were randomly assigned to either one dose of 1,000 mg (n=37) or 1,500 mg (n=37) ATX101, a control group (saline placebo (n=4)_, or bupivacaine standard of care active comparator (n=34)).

The bupivacaine comparator was administered once by way of local infiltration or adductor canal block; two or three 500 mg ATX101 implants were placed within the knee capsule prior to surgical closure. Opioids were used as needed for postoperative pain, and all patients received around-the-clock celecoxib and acetaminophen to simulate a real-world multimodal analgesic protocol.

David Hewitt, M.D., CMO of the study sponsor, Allay Therapeutics, told OTW, “Allay’s ATX101 product was designed by surgeons to ensure ease of administration, form factor that fits within anatomy and simplifies the surgical workflow. Yet it was then developed by scientists with a long history of drug elution technologies to safely deliver small amounts of drug in a controlled fashion over a long period.”

“The drug and polymer technology started in Singapore with Lightstone Singapore and the Foundry incubator (Menlo Park, CA) seeding and acquiring the technology and built Allay around those capabilities. Initially the team started with antibiotics and then moved to focus on post-surgical pain relief using bupivacaine, the mainstay of analgesic protocols and a well-defined Poly (lactic-co-glycolic acid) polymer. We then developed implants that treat the pain anatomically at the source, instead of pharmacologic approaches like opioids.”

“The results from the 112-patient Part A study against bupivacaine standard of care showed rapid and durable pain relief out through 30 days, with less opioids used, earlier opioid-free recovery, and never-before-seen functional improvements at 30 and 60 days.”

“These results will give patients a gentle active recovery, critical for successful long-term results after TKA. Clinicians will save time in their operating room with favorable reimbursement, and payers will benefit from less resource utilization. Importantly, we saw a favorable safety profile—by using a local anesthetic and polymers that are commonly used in surgery, we can hopefully demonstrate weeks of pain relief but without the development risk of many new chemical entities.”

“We now move into the final registration studies for FDA approval with a Phase 2B planned this year in the U.S., and a global Phase 3 against standard of care or leading competition that will take us to FDA approval in 2027. We have a pipeline of other products with different shapes, forms, and drug release to target other soft and hard tissue applications, all under a shared platform in Singapore and the U.S.”

The company indicates that this data informs the design of a pivotal Phase 2B study projected to start in 2024. If successful, this study would support a new drug application filed with the FDA.